Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice.

Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation of the adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulation of immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. We previously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibiting monocyte chemoattractant protein-1 (MCP-1) expression in the progression phase to high-fat diet (HFD)-induced obesity. In the current study, we evaluated the effects of naringenin on neutrophil infiltration into adipose tissue, because neutrophils also infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adipose tissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-induced expression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expression in 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did not affect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration and activation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppresses neutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.

Blockade of visfatin induction by oleanolic acid via disturbing IL-6-TRAF6-NF-κB signaling of adipocytes.

Oleanolic acid is a pentacyclic triterpenoid naturally present in foods and medicinal plants with anticancer, antioxidant, and antiaging properties. The current study elucidated that oleanolic acid inhibited the production of insulin-mimetic and inflammatory adipokine of visfatin during adipogenic differentiation of 3T3-L1 adipocytes. Adipocytes were cultured in an adipogenic media with and without 1-25 µM oleanolic acid up to 8 days for differentiation. The cellular expression and secretion of visfatin was markedly enhanced in differentiating adipocytes, which was dose-dependently attenuated by 1-25 µM oleanolic acid. Secretion of interleukin (IL)-6 and macrophage inflammatory protein (MIP)-2 was highly elevated during differentiation, which was much earlier than visfatin production of adipocytes. The visfatin production was secondary to inflammatory IL-6 and MIP-2. This study further elucidated that nuclear factor-κB (NF-κB) signaling was responsible for cellular production of visfatin. NF-κB was activated by translocating into the nucleus with increased phosphorylation of inhibitory κB (IκB), which was disturbed by oleanolic acid. Cellular expression of tumor necrosis factor receptor associated factor 6 (TRAF6), a NF-κB upstream, was upregulated in parallel with transactivation with NF-κB. The TRAF6 induction required the auto-stimulation of inflammatory IL-6 and MIP-2. These results demonstrate that oleanolic acid inhibited visfatin and its inflammatory response during adipocyte differentiation through blocking IL-6-TRAF6-NF-κB signaling. Therefore, oleanolic acid may be a potent therapeutic agent targeting against adipogenesis and visfatin-linked inflammation.

Berberine attenuates cigarette smoke-induced acute lung inflammation.

Berberine (Ber), the major constituent of Coptidis Rhizoma, possesses anti-inflammatory properties. In this study, we investigated the effects of Ber on cigarette smoke (CS)-mediated acute lung inflammation. C57BL/6 mice (6-8 weeks) were exposed to CS to induce acute lung injury. Ber was used to pretreat CS-exposed mice (50 mg/kg, intragastrically). Lung tissues were collected for histological examination, myeloperoxidase (MPO) activity assay, Western blot analysis, and electrophoretic mobility shift assay. Bronchoalveolar lavage fluid (BALF) was measured for cell counts and cytokine analysis. Histological examination showed that CS exposure caused infiltration of inflammatory cells into alveolar spaces and interstitial edema. Pretreatment with Ber significantly attenuated CS-induced lung inflammation. The numbers of total cells, macrophages, and neutrophils in BALF were decreased by 43, 40, and 53 %, respectively, by Ber pretreatment in CS-exposed mice, accompanied by decreased MPO activity, a marker of neutrophil accumulation. Ber pretreatment also profoundly diminished CS-induced secretions of macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-6, and monocyte chemotactic protein-1 in BALF, along with less nuclear translocation of the pro-inflammatory transcription factor nuclear factor-kappa B (NF-κB) p65 subunit and lower NF-κB DNA-binding activity (P < 0.01). Thus, our results indicated that Ber ameliorates CS-induced acute lung injury through its anti-inflammatory activity.

Beta-carotene prevents ozone-induced proinflammatory markers in murine skin.

Beta-carotene has been thought to protect against oxidative stress generated by ultraviolet radiation and thus prevents skin cancer and skin aging (Biesalski and Obermueller-Jevic, 2001). However, nothing is known about its potential effects against other environmental sources of oxidative stress such as ozone (O3) in skin. Intake of oral beta-carotene supplements before exposure to sunlight (and thus inevitably also to (O3) has been recommended on a population-wide basis. However, although some studies have shown beta-carotene as providing skin protection as an antioxidant, other studies using skin cells in culture have shown that beta-carotene may have unexpected prooxidant properties (Obermüller-Jevic, et al., 2001). Given this, there is an ongoing debate regarding the protective or potentially harmful role(s) of beta-carotene in human skin. In this study, the effect of beta-carotene on ozone's effects on the skin of hairless mice was assessed. After feeding a diet supplemented with 0.5% beta-carotene for 1 month, mice were subjected to O3 exposure (0.8 ppm 6 h/day; 7 days) and the induction of proinflammatory markers such as tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein 2 (MIP2), and inducible nitric oxide synthase (iNOS), and markers of oxidative stress, heme-oxygenase-1 (HO-1), were quantitated. The data showed that beta-carotene downregulated the induction of TNFalpha, MIP2, iNOS, and HO-1 in response to O3. We conclude that beta-carotene provides protection against O3-induced skin oxidative stress in vivo, which is consistent with a protective role for beta-carotene in the skin.